title: (17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester (YK11) is a partial agonist of the androgen receptor.
abstract: A novel steroid compound, (17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester (YK11), was found to be a partial agonist of the androgen receptor (AR) in an androgen responsive element (ARE)-luciferase reporter assay. YK11 accelerates nuclear translocation of AR. Furthermore, YK11 does not induce amino/carboxyl-terminal (N/C) interaction and prevents 5-α-dihydrotestosterone (DHT)-mediated N/C interaction. Thus, YK11 activates AR without causing N/C interaction, which may in turn be responsible for the partially agonistic nature of YK11 observed in the ARE-luciferase reporter system. YK11 acts as a gene-selective agonist of AR in MDA-MB 453 cells. The effect of YK11 on gene expression relative to that of androgen agonist varies depending on the gene context. YK11 activated the reporter gene by inducing the translocation of the AR into the nuclear compartment, where its amino-terminal domain (NTD) functions as a constitutive activator of AR target genes. Our results suggest that YK11 might act as selective androgen receptor modulator (SARM).
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba 274–8510, Japan. Funabashi, Chiba 274–8510, Japan. ykanno@phar.toho-u.ac.jp
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kanno
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Hikosaka
authors.forename: Shu-Yun
authors.initials: SY
authors.lastname: Zhang
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakahama
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kato
authors.forename: Akemi
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tominaga
authors.forename: Shinya
authors.initials: S
authors.lastname: Kohra
authors.forename: Koji
authors.initials: K
authors.lastname: Arizono
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Inouye
mesh_terms: D000728:Androgens / Q000138:chemical synthesis / Q000494:pharmacology*; D001692:Biological Transport; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D009649:Norpregnadienes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*
chemical_list: C562327:17,20-((1-methoxyethylidene)bis(oxy))-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester; D000728:Androgens; D009649:Norpregnadienes; D011944:Receptors, Androgen